The aim was to perform an umbrella review to summarise the existing evidence on proton-pump inhibitor (PPI) use and adverse outcomes and to grade the certainty of evidence.Methods: Electronic databases were searched up to July 2021 for meta-analyses of cohort studies and/or randomised controlled trials (RCTs). Summary effect sizes from a random-effects model, between-study heterogeneity, 95% prediction interval, small-study effect, excess significance and credibility ceilings were devised to classify the credibility of evidence from meta-analyses of cohort studies, whereas the GRADE approach was used for meta-analyses of RCTs.Results: In meta-analyses of cohort studies, 52 of the 91 examined associations were statistically significant (P ≤ .05). Convincing evidence emerged from main analysis for the association between PPI use and risk of all-site fracture and chronic kidney disease in the elderly population. However, none of these associations remained supported by convincing evidence after sensitivity analyses. The use of PPI is also associated with an increased risk of mortality due to COVID-19 infection and other related adverse outcomes, but the quality of evidence was weak. In meta-analyses of RCTs, 38 of the 63 examined associations were statistically significant. However, no associations were supported by high or moderate-quality evidence.Conclusion: This study's findings imply that most putative adverse outcomes associated with PPI use may not be supported by high-quality evidence and are likely to have been affected by underlying confounding factors. Future research is needed to confirm the causal association between PPI use and risk of fracture and chronic kidney disease.

This umbrella review aims to summarize the effects of Aloe vera on health outcomes and assess the strength of evidence. PubMed, Scopus, Embase, Cochrane database of systematic reviews, CINAHL, and AMED were searched from inception to October, 2019 for systematic reviews and meta‐analyses of clinical trials that investigated the effects of Aloe vera on health outcomes. Two independent reviewers extracted data, assessed the methodological quality, and rated the credibility of evidence according to established criteria. Ten articles reporting 71 unique outcomes of Aloe vera were included. Of these, 47 (67%) were nominally statistically significant based on random‐effects model (p ≤ .05). Only 3 outcomes were supported by highly suggestive evidence, whereas 42 outcomes were supported by weak evidence. The highly suggestive evidence supported benefits of Aloe vera in the prevention of second‐degree infusion phlebitis (RR: 0.18, 95% CI: 0.10–0.32, p‐value: 1.75 × 10−9) and chemotherapy‐induced phlebitis based on overall incidence (OR: 0.13, 95% CI: 0.08–0.20, p‐value: 9.68 × 10−20) and incidence of the second degree of severity (OR: 0.10, 95% CI: 0.07–0.14, p‐value: 3.41 × 10−35). However, the majority of the evidence were limited by small sample size and poor methodological quality. Therefore, despite the overall favorable effect of Aloe vera, more robust studies are needed.

Introduction The number of umbrella reviews (URs) that compiled systematic reviews and meta-analysis (SR-MAs) has increased dramatically over recent years. No formal guidance for assessing the certainty of evidence in URs of meta-analyses exists nowadays. URs of non-interventional studies help establish evidence linking exposure to certain health outcomes in a population. This study aims to identify and describe the methodological approaches for assessing the certainty of the evidence in published URs of non-interventions. Methods We searched from 3 databases including PubMed, Embase, and The Cochrane Library from May 2010 to September 2021. We included URs that included SR-MAs of studies with non-interventions. Two independent reviewers screened and extracted data. We compared URs characteristics stratified by publication year, journal ranking, journal impact factor using Chi-square test. Results Ninety-nine URs have been included. Most were SR-MAs of observational studies evaluating association of non-modifiable risk factors with some outcomes. Only half (56.6%) of the included URs assessed the certainty of the evidence. The most frequently used criteria is credibility assessment (80.4%), followed by GRADE approach (14.3%). URs published in journals with higher journal impact factor assessed certainty of evidence than URs published in lower impact group (77.1 versus 37.2% respectively, p < 0.05). However, criteria for credibility assessment used in four of the seven URs that were published in top ranking journals were slightly varied. Conclusions Half of URs of MAs of non-interventional studies have assessed the certainty of the evidence, in which criteria for credibility assessment was the commonly used method. Guidance and standards are required to ensure the methodological rigor and consistency of certainty of evidence assessment for URs.

This study aims to summarize the effects of herbs on dementia and assess the strength of evidence. Six international and local databases were searched from inception to October 2021 for systematic reviews and meta‐analyses of clinical trials investigated the effects of herbal medicine on dementia or cognitive function. Two researchers independently extracted data, assessed the methodological quality, and rated the credibility of evidence according to established criteria. Thirty‐seven articles evaluating 13 herbal medicines were included. Of these, 65% were rated critically low using AMSTAR2. Of 90 unique outcomes, 41 (45.6%) were statistically significant based on random effects model (p ≤ .05). Only 3 herbs were supported by suggestive evidence whereas the others were supported by weak evidence. The suggestive evidence supported benefits of Chinese herbal medicine (CHM) plus pharmacotherapy (WMD:1.84; 95% CI: 1.34, 2.35) and Vinpocetine (WMD: −0.94; 95%CI: −1.50, −0.38) on improving cognitive function assessing by Montreal Cognitive Assessment and Syndrom‐Kurz‐Test, respectively. Moreover, suggestive evidence supported benefit of Huperzia serrata on improving Activities of Daily Living (WMD:‐7.18; 95%CI: −9.12, −5.23). No SAE was reported. In conclusion, several herbs were used for improving dementia and cognitive function but recent evidence were limited by the small sample size and poor methodological quality. Therefore, further large and well‐designed studies are needed to support the evidence.

Objective: To identify and describe the methodological approaches for assessing the certainty of the evidence in umbrella reviews (URs) of meta-analyses (MAs).Study Design and Setting: We included URs that included SR-MAs of interventions and non-interventions. We searched from 3 databases including PubMed, Embase, and The Cochrane Library from 2010 to 2020.Results: 138 URs have been included consisting of 96 and 42 URs of interventions and non-interventions, respectively. Only 31 (32.3%) of URs of interventions assessed certainty of evidence, in which the GRADE approach was the most frequently used method (N=20, 64.5%) followed by creditability assessments (N=6, 12.9%). Conversely, thirty (71.4%) of URs of non-interventions assessed certainty of evidence, in which the criteria for credibility assessment were mainly used (N=28; 93%). URs published in journals with high journal impact factor (JIF) are more likely to assess certainty of evidence than URs published in low JIFs. Conclusions: Only one-third of URs that included MAs of experimental designs have assessed the certainty of the evidence in contrast to the majority of the URs of observational studies. Therefore, guidance and standards are required to ensure the methodological rigor and consistency of certainty of evidence assessment for URs.